Acupuncture, Herbs, Nutrients and Foods for Bone Health

Posted on August 19, 2017 by John & Barbara Connor

by Barbara Connor, M.Ac., L.Ac.  

I would like to share with you today studies on the benefits of acupuncture, nutrients, herbs, foods and exercise in building strong bones.  I hope you find this article useful in appreciating the value of acupuncture, certain nutrients, herbs and foods as well as exercise in your quest for optimal bone health.

Table of Contents

  • Introduction
  • Studies on the Benefits of Acupuncture  for Bone Health
  • Beneficial Nutrients, Herbs and Foods for Bone Health
  • Studies on Beneficial Nutrients, Herbs and Foods for Bone Health
  • Studies on the Beneficial Effects of Exercise on Bone Mineral Density
  • Studies on the Relationship between Vitamin D and Bone Mineral Density
  • Studies on the lmportance of Combining Vitamin D with Vitamin K
  • Studies on Other Issues Concerning Bone Health

Introduction

Almost 30 million Americans are affected by osteoporosis, and women are 4 times more likely to suffer from this disease than men. (Kerstetter et al 2003) Fractures associated with this disease affect one in three women and one in five men over the age of 50 years. (Sacco et al 2013)

Women are vulnerable to increased bone loss during and after menopause. Maintenance of bone health with aging is attributed to genetics, sun exposure (maintaining vitamin D levels), exercise and diet. (Gunn et al 2015) PMID: 25856221

Of interest to the bone field is the number of population-based studies published in the latter part of the 20th century, and between 2001 and 2006, which have demonstrated a consistent, beneficial effect of fruit and vegetable intake on indices of bone health across a wide range of age groups including young boys and girls, premenopausal women, perimenopausal and postmenopausal women, and elderly men and women. (Lanham-New S 2008) Cross-sectional studies have shown a positive association between higher fruit intake and higher bone mineral density. (Shen et al 2012) PMID: 23244535

A bone protective diet can be characterized as a diet rich in fruits and vegetables, dairy products, seeds and nuts, whole grain and soy products and moderate amounts of fish, eggs and lean meat. This diet provides sufficient amounts of protein, calcium, magnesium and vitamins (e. g. K, C, folic acid, B6 and B12), which are important for bone development. (Strohle & Hahn 2016)

Bone is constantly being remodeled in a dynamic process where cells called osteoblasts form new bone and cells known as osteoclasts break down bone tissue.

The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis (the development of osteoclasts from blood cells) and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). (An et al 2016) PMID: 27131574 

The two nutrients essential for bone health are calcium and vitamin D. Reduced supplies of calcium are associated with a reduced bone mass and osteoporosis, whereas a chronic and severe vitamin D deficiency leads to osteomalacia, a metabolic bone disease characterized by a decreased mineralization of bone.  The main sources of calcium in the diet are dairy products (milk, yoghurts and cheese) fish (sardines with bones), few vegetables and fruits. The optimal way to achieve adequate calcium intake is through the diet. However, when dietary sources are scarce or not well tolerated, calcium supplementation may be used. (Gennari C 2001) PMID: 11683549

In patients with low calcium intake supplements are warranted aiming for a total calcium intake of 800 to 1000 mg/d together with adequate vitamin D replacement. (Meier & Kranzlin 2011)

Calcium supplementation is only for those unable to get enough calcium in their diet. Examples of foods high in calcium include yogurt (415 mg/serving), mozzarella, sardines with bones, cheddar cheese, milk; salmon pink, canned, solids with bone; cottage cheese, turnip greens, kale (94 mg/serving).  (NIH Office of Dietary Supplements website)

Many factors influence bone mass. Protein has been identified as being both detrimental and beneficial to bone health, depending on a variety of factors, including the level of protein in the diet, the protein source, calcium intake, weight loss, and the acid/base balance of the diet. (Heaney & Layman 2008) PMID: 18469289  There is agreement that diets moderate in protein (in the approximate range of 1.0–1.5 g protein/kg) are associated with normal calcium metabolism and presumably do not alter skeletal homeostasis. (Kerstetter et al 2003)

With regard to calcium and vitamin D, the International Osteoporosis Foundation recommends a daily intake of 1200 mg calcium and 800–1000 IU vitamin D for postmenopausal women. Elderly women, or those with reduced physical activity and sunlight exposure, may need higher levels of these nutrients. For these high-risk for fracture individuals, the measurement of 25-OH Vitamin D levels is recommended and high dose vitamin D supplementation given if deficient. For other postmenopausal women receiving aromatase inhibitor (AI) therapy, a dose of at least 800 (and up to 2000) IU of vitamin D every day is recommended to maintain replete levels. (Hadji et al 2017) PMID: 28413771

In general, calcium from food is as well absorbed as calcium supplements, but there are differences in bioavailability. Some foods decrease calcium absorption, such as oxalic acid (spinach, collard greens, sweet potatoes, rhubarb and beans), or phytic acid (fiber-containing whole-grain products and wheat bran, beans, seeds, nuts and soy isolates). Others enhance calcium absorption, such as lactose and certain caseinophospho peptides formed during digestion of caseins from milk. This explains—for instance—the high availability of calcium in broccoli and kale, which is low in oxalate, and the low availability of calcium in spinach, which is rich in oxalate. Therefore, equivalent calcium contents do not guarantee equivalent nutritional values. (Bruckhardt P 2015)

Total homocysteine (tHcy) is negatively associated with bone mineral density (BMD) of the total femur. The contribution of tHcy to explain the variance of BMD is small (2% of the total variance) but clinically relevant, considering the high prevalence of osteoporosis among post-menopausal women and the possibility to lower tHcy by vitamin supplementation. (Bucciarelli et al 2010) PMID: 20603040

Studies on the Benefits of Acupuncture on Bone Health

In Chinese Medicine osteoporosis is recognized as an aging and degenerative condition caused by insufficiency of Kidney Qi in line with the theory of traditional Chinese medicine (TCM) in the ancient book of the Inner Canon of Huangdi , and acupuncture as well as herbs have been widely applied to treat it for the past 2000 years. (Guo et al 2016)

In Chinese Medicine the Kidneys govern the bone marrow (a substance which is the common matrix of bones, bone marrow, brain and spinal cord) and bones. If the Kidney-Essence is strong, the bones will be strong. (Maciocia, The Foundation of Chinese Medicine, page 96)

  1. Eighty-five postmenopausal patients were randomly divided into an observation group (43 cases) and a control group (42 cases). Both groups were treated with oral administration of caltrate-D tablet, 600 mg per day.  After treatment, the BMD in the observation group was significantly increased; the improvement in the observation group was more significant than that in the control group (all P<0. 05). After treatment, the index of bone metabolism in the control group was increased, and the serum bone gla protein, the hydroxyproline/creatinine in the control group were higher than those in the observation group (both P<0. 05). The authors conclude that the treatment of warm needling combined with element calcium on postmenopausal osteoporosis is significant, which is likely achieved by reducing the bone metabolism of postmenopausal patients. (Cai et al 2015) PMID: 26721135
  2. The clinical effect of acupuncture combined with TDP for treatment of postmenopausal patients with deficiency of liver and kidney syndrome is significant, and it can increase bone mineral density, decrease endometrial thickness and obviously regulate the estrogen level. (Wang JF 2009) PMID: 19947264
  3. The therapeutic effect of warm needle moxibustion on osteoporosis is better than that of oral administration of tablet Caltrate with Vit D2 and it can increase levels of hormones and delay bone loss. It is an effective method for preventing and treating postmenopausal osteoporosis. (Zhao et al 2008) PMID: 19127918
  4. A rapid lowering of the bone mass in postmenopausal women is also related to the lowered gastrointestinal absorption capacity for calcium and other nutrient substances due to hypo function of the various systems with ageing. Therefore, Caltrate D was administer to this series of patients. The therapy with acupuncture plus drug has a been shown to significantly increase the bone mineral density (P<0.01), with a therapeutic effect much superior to that of the control group (P<0.05). (Ouyang et al 2002)

Beneficial Nutrients, Herbs and Foods for Bone Health

  1. Beta-carotene, vitamin C, zinc and sodium
  2. Boron
  3. Calcium
  4. Dairy products
  5. Dried plums
  6. Epidmedii herba
  7. Fish oil
  8. Lactoferrin
  9. Magnesium
  10. Mediterranean diet
  11. Omega-3 fatty acids
  12. Sodium
  13. Ursolic acid
  14. Vitamin C
  15. Vitamin D
  16. Yogurt
  17. Zinc

Studies on Beneficial Nutrients, Herbs and Foods for Bone Health
Beta-carotene, vitamin C, zinc and sodium – In postmenopausal Korean women, β-carotene, vitamin C, zinc and sodium intakes were positively associated with bone mass. Furthermore, frequency of vegetable consumption was positively associated with femoral neck and total hip T-scores. (Kim et al 2016) PMID: 27664069

Boron – There is a suggestion that boron may increase the efficacy or utilization of vitamin D. Indeed, it has been reported that boron can alleviate marginal vitamin D deficiency. (Jugdaosingh et al 2015) PMID: 26665155

Calcium – Adequate calcium intake is essential for normal growth and development of the skeleton and teeth and for adequate bone mineralization. Optimizing bone mass accretion in youth and adolescence is critical to attaining peak bone mass in adulthood. In adulthood, low calcium intake has been associated with increased risk for osteoporosis, bone fractures, and falls. (Bailey et al 2010) 

Calcium – Adequate intakes of calcium and vitamin D are essential preventive strategies and essential parts of any therapeutic regimen for osteoporosis. However, calcium supplementation is not without controversy and benefits on skeletal health need to be balanced against potential risks on cardiovascular disease. The published data so far suggest a potential detrimental effect of calcium supplement on cardiovascular health (i.e. myocardial infarction) although further prospective studies are needed to clarify the gradient of risk. Since food sources of calcium produce similar benefits on bone density as supplements and dietary calcium intake does not seem to be related with adverse cardiovascular effects, calcium intake from nutritional sources needs to be enforced. (Meier & Kranzlin 2011) PMID: 21882122

Dairy products – In this study of elderly black and white men and women, dairy nutrients contributed significantly and interchangeably to a predictive model of total hip and femoral neck BMD that included weight, age, race, and sex. Milk was the primary source of calcium in all groups. All subjects ingested calcium at intakes well below the requirement for this age group, but the insufficiency was least in the black men. Dairy consumption predicted total hip BMD in the black men but not in the white men and not in the women of either race. Nevertheless, a calcium supplementation intervention was equally effective in protecting against bone loss in the white men and women. Elderly persons who had lower previous dairy intakes and who were younger than 72 y experienced the greatest positive benefit of calcium supplementation. Overall, this study suggests a positive role for dairy foods in the diet of the elderly. (McCabe et al 2004) PMID: 15447921

Dried Plums – These results confirm the ability of dried plums to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50 g) may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. (Hooshmand et al 2016) PMID: 26902092

Epimedii herba – is one of the most frequently used herbs in formulas prescribed for the treatment of osteoporosis in China. The main active flavonoid glucoside extracted from Epimedium pubescens is icariin, which has been reported to enhance bone healing and reduce osteoporosis occurrence. In this study, we demonstrate that in vitro icariin is a bone anabolic agent that may exert its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfa1/Runx2, OPG, and RANKL gene expressions. This effect may contribute to its action on the induction of osteoblasts proliferation and differentiation, resulting in bone formation. (Hsieh et al 2010)

Fish oil – Findings from human studies largely show that greater intake of total polyunsaturated fatty acids (PUFAs), total n–6 PUFAs, total n–3 PUFAs, and fish is associated with higher BMD or lower risk of fragility fracture in women. Less consistent benefits to bone health are associated with higher intake of long chain n–3 PUFAs or when the dietary ratio of n–6 to n–3 PUFAs is considered. The strongest evidence for benefits to bone is from studies of fish intake. Regular consumption of fish and seafood not only provides high quantities of PUFAs but can also be rich sources of protein, vitamin D, calcium, and other vitamins and minerals, all of which are necessary for the maintenance of strong, fracture-resistant bones. (Longo & Ward 2016) PMID: 26098476

Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated. (Wlodarski et al 2014) PMID: 25154204 

Lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth. (Cornish et al 2004) PMID: 15166119

Lactoferrin is an anabolic peptide that has been proven to induce bone growth in vivo. Cornish et al. have suggested that lactoferrin acts on bone cells at periphysiological concentrations and might have a therapeutic role for bone repair. The data from the current study indicate that a combination of 3 mg of bovine lactoferrin-loaded gelatin microspheres and bovine-derived hydroxyapatite promotes bone regeneration in defects around implants. (Gormez et al 2015)

Lactoferrin inhibits formation of osteoclasts (which break down bone) and stimulates formation of osteoblasts (which build bone.) The results of one animal study suggest that bovine lactoferrin treatment could promote bone regeneration during distraction osteogenesis in the test animal. The results indicate that the OPG/RANKL/RANK system might be a major mechanism for increased bone formation and decreased bone resorption in distraction osteogenesis with bovine lactoferrin treatment. (Li et al 2015)

Magnesium – is an important contributor to bone health. In several studies on animals, dietary magnesium restriction promotes osteoporosis, fragility, microfractures of the trabeculae and reduction of bone’s mechanical properties. Dietary sources of magnesium include almonds, cashews and peanuts, raisin bran cereal, potato skins, brown rice, kidney beans, black-eyed peas and lentils. A modest supplementation with 250 mg/day of magnesium is reasonable to support bone health.  (Pepa & Brandi 2016) PMID: 28228778

A note about magnesium – Since magnesium (Mg) is a calcium antagonist it is feasible to propose that high concentrations of magnesium alter calcium/Mg ratio, thus leading to dysregulated cell functions. Accordingly, an in vitro inhibitory effect of high Mg on osteoblast differentiation and mineralizing activity has been shown. (Castiglioni et al 2013) PMID: 23912329 However, in a study on bone-related minerals during denosumab (Prolia) administration in post-menopausal osteoporotic patients it was concluded that since denosumab may not improve Mg, it is better to obtain Mg supplementation during the therapy. (Suzuki et al 2017) PMID: 28805705

Mediterranean diet – The results demonstrate a positive correlation between bone health status and adherence to Mediterranean diet (MD), suggesting that a high adherence to MD promotes bone health. The observations here reported confirmed that a specific dietary approach, such as MD, can represent a modifiable environmental factor for osteoporosis prevention. (Savanelli et al 2017) PMID: 28438173

Omega-3 fatty acids (FAs) – A higher dietary ratio of omega-6 to omega-3 FAs was associated with lower hip bone mineral density (BMD) in 1532 community-dwelling subjects aged 45–90 years. The ratio of dietary LA to ALA was inversely associated with hip BMD, independently of hormone therapy. A higher ratio of total dietary omega-6 to omega-3 FAs was also associated with lower BMD at the spine in women not undergoing hormone therapy and at the hip in all women. In summary, bone health is significantly correlated with omega-3 status. (Molfino et al 2014)

Sodium – Hyponatremia (low sodium) directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. (Negri & Ayus 2017) PMID: 27664044

Ursolic acid – The results of this in vivo study suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation. (Lee et al 2008) PMID: 18822379 

Ursolic acid – The results of another in vivo study suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation, enhance new bone formation, and suppress absorptive function of osteoclast. (Yu et al 2015) PMID: 26097549

Vitamin C – Higher vitamin C intake levels were associated with a lower risk of osteoporosis in Korean adults aged over 50 with low levels of physical activity. However, no association was seen between vitamin C intake and osteoporosis risk in those with high physical activity levels. (Kim & Lee 2016) PMID: 27134348

Vitamin D3 is fat soluble and is stored in the body fat. Vitamin D deficiency results in abnormalities in both calcium and phosphorus metabolism. The major function of vitamin D is to maintain serum calcium concentrations within the physiologically acceptable range. It accomplishes this by increasing intestinal calcium absorption. In a vitamin D-deficient state, the intestine typically absorbs 10-15% of dietary calcium. In a vitamin D-sufficient state, 30% typically is absorbed from the diet; as much as 60-80% can be absorbed during periods of growth and pregnancy or lactation, with increased demand for calcium. (Holick M 2004)

Vitamin D in the human body is mainly derived from skin after ultraviolet light exposure and from dietary sources.  There are two main forms of Vitamin D, Vitamin D3 (cholecalciferol) and Vitamin D2 (ergocalciferol). Currently the biological effects of Vitamin D are divided into two categories: First, in calcium and phosphorus metabolism, considered the classical activity; and second, the non-classical or alternative pathway that mainly affects immune function, inflammation, anti-oxidation, anti-fibrosis and others, as wells as inhibitory effects on the many kinds of malignancies. (Wang et al 2017)

Yogurt – In this cohort, higher yogurt intake was associated with increased BMD and physical function scores. These results suggest that improving yogurt intakes could be a valuable public health strategy for maintaining bone health in older adults. (Laird et al 2017) PMID: 28462469

Zinc has been considered an important factor in bone metabolism since bone contains approximately 30% of the zinc in the body. Zinc has been known to promote bone formation and inhibit bone resorption in in vitro studies. In a previous study, we demonstrated that dietary zinc deficiency decreased bone formation and increased bone resorption in rats. (Suzuki et al 2016) PMID: 27013778 

Studies on the Relationship between Vitamin D and Bone Mineral Density

  1. Vitamin D deficiency coexists with low bone mineral density (BMD) in our study group. Serum 25(OH)D needs to be documented in women having low BMD. Calcium and vitamin D need to be supplemented as part of therapy in post-menopausal women. (Harinarayan et al 2011)
  2. Vitamin D3 & Calcium – Combined calcium and vitamin D3 supplementation was effective in reducing the rate of bone mineral density loss in women with moderate chronic kidney disease. (Bosworth et all 2012)
  3. Vitamin D – In utero and during childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults can exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, and increase the risk of fracture. (Szabo A 2011)
  4. Vitamin D – In addition to enhancing calcium absorption from the intestine and mineralization of the osteoid tissue, vitamin D has many other physiological effects, including neuromodulation, improving muscle strength and coordination, insulin release, immunity and prevention of infections, and curtailing cancer. (Wimalawansa SJ 2011)
  5. Vitamin D plays a major role in bone mineral homeostasis by promoting the transport of calcium and phosphate to ensure that the blood levels of these ions are sufficient for the normal mineralization of type I collagen matrix in the skeleton. (Haussler et al 1997)

Studies on the lmportance of Combining Vitamin D with Vitamin K

  1. Vitamin K acts synergistically with Vitamin D on bone mineral density (BMD) and positively influences the balance of calcium, a key mineral in bone metabolism.  Addition of vitamin K to vitamin D and calcium supplements in postmenopausal Korean women increases the L3 BMD and reduces the undercarboxylated osteocalcin concentration.(Sang Hyeon Je et al 2011)
  2. Vitamin D with K1 promotes beneficial effects on the elastic properties of arterial vessel walls: It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall. (Braam et al 2004)

The presence of calcification in any arterial wall is associated with a 3-4-fold higher risk for mortality and cardiovascular events. (Rennenberg et al 2009)

  1. Vitamin D3 and K2 induce mineralization in human osteoblasts: In the present study, it was demonstrated that the vitamin K metabolic cycle functions in human osteoblasts as well as in the liver, the post-translational mechanism, by which 1,25(OH)2D3 caused mineralization in cooperation with vitamin K2 was clarified. (Miyake et al 2001)

The 1,25(OH)2D3-induced mineralization promoted by vitamin K2 was probably due to the enhanced accumulation of osteocalcin induced by vitamin K2 in the cell layer. These results suggest that the mechanism underlying the mineralization induced by vitamin K2 in the presence of 1,25(OH)2D3 was different from that of vitamin K2 alone, and that osteocalcin plays an important role in mineralization by osteoblasts in vitro. (Koshihara et al 1996)

Both types of vitamin K treatment – menaquinone-4 (MK-4) and vitamin K(1) – decreased the expression of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor and enhanced the expression of osteoprotegerin/osteoclast inhibitory factor in the stromal cells. Vitamin K might stimulate osteoblastogenesis in bone marrow cells. (Koshihara et al 2003)

  Studies on the Beneficial Effects of Exercise on Bone Mineral Density

  1. We report significant improvements in bone mineral density (BMD) at the spine, hip, and whole body for female cancer survivors who completed 26 weeks of combined aerobic and resistance-training (CART). This investigation demonstrates the possible effectiveness of CART at improving bone health and reducing risk of osteoporosis for women who have completed cancer treatment. The Improving Physical Activity After Cancer Treatment (IMPAACT) Program appears to be a safe and feasible way for women to improve health after cancer treatment. (Almstedt et al 2016) PMID: 28580396
  2. Women who began training with the lowest initial values had the greatest improvements in hip bone mineral density (BMD), hip abductor strength, leg power, and postural stability. These results support the training principle of initial values and suggest that this training program may be most successful in premenopausal women with lower values of musculoskeletal indices of fracture risk. (Winters-Stone & Snow 2003) PMID: 14523306
  3. A 5-year program of weighted vest plus jumping exercise maintains hip bone mineral density (BMD) by preventing significant bone loss in older postmenopausal women. Furthermore, this particular program appears to promote long-term adherence and compliance, as evidenced by the commitment of the exercisers for more than 5 years. (Snow et al 2000) PMID: 10995045
  4. This study provides the first evidence that low-repetition, light-load power training significantly increases pelvis BMD in postmenopausal women with sarcopenia. Since this training program does not require high-load exercise, high levels of adherence would be anticipated due to its ease of implementation. We conclude that low repetition, light-load power training would be an effective form of training exercise for sedentary adults who are at risk for osteoporosis and wary of heavy loads and/or fatigable training. (Hamaguchi et al 2017) PMID: 28464798

Studies on Other Issues Concerning Bone Health

    1. Be aware of medications that can increase fracture risk – Drug-induced osteoporosis is a type of secondary osteoporosis. Glucocorticoids are the most common cause of drug-induced osteoporosis. But other drugs can increase fracture risk, such as thyroxine overdose, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, thiazolidines, proton pump inhibitors, loop diuretics, anticoagulant drugs, selective serotonin reuptake inhibitors (SSRI) , tricyclic antidepressants, anticonvulsants, and so on. (Suzuki H 2013)
    2. Do not smoke – It is suggested that the number of hip fractures in the world will increase from 1.66 million in 1990 to 6.26 million by 2050. There is a demonstrated research show that approximately 19% of all hip fractures were attributed to cigarette smoking, and the relative risk for current smokers comparing with never smokers was consistently higher in males than in females. (Wu et al 2016) PMID: 28036356
    3. Avoid high intake of cola – This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study. (Kristensen et al 2005) PMID: 15886860

*****

Compassionate Acupuncture and Healing Arts, providing craniosacral acupuncture, herbal and nutritional medicine in Durham, North Carolina. Phone number 919-475-1005

 

      Posted in acupuncture, bone health, botanical medicine, chronic conditions, dietary recommendations, exercise, foods, herbal medicine, nutritional medicine, osteoporosis, Traditional Chinese Medicine | Tagged , , , , , | Leave a comment

      Quorum Sensing and Biofilm Formation and Natural Compounds that Disrupt these Processes

      Posted on January 10, 2016 by John & Barbara Connor

      by John & Barbara Connor, M.Ac., L.Ac.

      Introduction
      What is Quorum Sensing?
      What are Biofilms?
      Rationale for Using Anti-Quorum Sensing and Biofilm Disrupting Natural Compounds
      Anti Quorum Sensing and Biofilm Disrupting Herbs, Spices, Foods and Essential Oils

      Introduction
      While researching the problem of antibiotic resistance John and I gained insight into the significance of the phenomena known as quorum sensing and biofilm formation. We would like to share with you some of the studies we came across on these two processes and their relationship to bacterial infections. We would also like to share with you some of the studies we have found that have been done on herbs, spices, foods and essential oils that can inhibit quorum sensing and disrupt biofilm formation. 

      Alarming trends in the spread of antibiotic resistance among top pathogens, including Staphylococcus aureus, have placed mankind at the brink of what has been coined as the ‘post-antibiotic era’. Since the widespread introduction of antibiotics in the 1940s, the same storyline has repeated itself over and over again: a new antibiotic is introduced and then resistant variants emerge and quickly spread, effectively limiting the utility and lifespan of the drug. (Quave et al 2015)

      As is well known, the major cause of mortality and morbidity in human beings is bacterial infection. However, bacteria have developed resistance to most of the antibiotics primarily due to large-scale and indiscriminate usage. (Kailia et al 2014)

      What is Quorum Sensing?

      Quorum sensing (QS) refers to the capacity of bacteria to monitor their population density and regulate gene expression accordingly: the QS-regulated processes deal with multicellular behaviors (e.g. growth and development of biofilm), horizontal gene transfer and host-microbe (symbiosis and pathogenesis) and microbe-microbe interactions. (Grandclement et al 2015)

      The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing inhibition strategies instead of bactericidal and bacteriostatic approaches. (Gemiarto et al 2015)

      The QS mechanism enables bacteria to detect their population density through the production, release, and perception of small diffusible molecules called autoinducers and to coordinate gene expression accordingly. A wide array of functions in bacteria ranging from bacterial cell motility to complex behaviors such as biofilm formation and production of virulence factors are regulated by QS in pathogenic bacteria.  (Husain et al 2015)

      Typical QS involves the generation and release of small diffusible signal molecules—autoinducers; they accumulate in the environment to a certain threshold concentration, followed by recognition by receptor proteins that regulate the expression of a particular set of genes and control manifold activities. Since this mechanism is responsible for bacterial virulence induction, QS targeting could be a promising strategy to control pathogenic bacteria, and some medicinal plants are capable of inhibiting QS-related processes. (Deryabin & Tolmacheva 2015)

      Quorum sensing cell communication is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. (Castillo-Juarez  et al 2015)

      Quorum sensing along with subversion of the immune system are the main factors that determine the bacterial infectious doses. Hence those bacterial pathogens that need small doses to infect, generally lack QS systems but are very effective at inactivating the immune response by killing professional phagocytes. In contrast, those bacterial pathogens that need high infectious doses rely on QS for the coordination of the expression of virulence. (Castillo-Juarez  et al 2015)

      Several bacterial pathogens, like Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Vibrio cholerae, utilize quorum sensing cell communication to coordinate the expression of multiple virulence factors and associated behaviors such as swarming and biofilm formation, once a population size threshold is reached. (Castillo-Juarez  et al 2015)

      What are Biofilms?

      Biofilms can be defined as structured aggregation of surface-attached microorganisms encased in an extracellular matrix. In all these [four] phases of biofilm formation, quorum-sensing system is involved in the regulation of population density and metabolic activity. (Chung & Toh 2014)

      Biofilms are responsible for most chronic and recurrent infections. Biofilm-related infections reoccur in approximately 65-80% of cases. Bacteria associated with the biofilm are highly resistant to antibiotics. (Venkatesan et al 2015)

      Biofilms are colonies of bacteria encased within extracellular polymeric matrix. Sessile (immobile) biofilm bacteria are phenotypically different than planktonic (drifting or floating) bacteria, conferring increased resistance to desiccation, antibiotics, and the immune response. Antibiotics are able to kill the planktonic cells released by the biofilm after its maturation stages, but bacteria within the biofilm can persist, causing chronic infections. In biofilm formation, bacteria attach reversibly to a surface, and then begin to produce extracellular polysaccharides. As the bacterial number grows, quorum sensing allows a phenotypic change in the bacteria. The biofilm matures and grows. Eventually, proteins break down parts of the matrix so that bacteria within the biofilm can disperse. (Ulrey et al 2014)

      About 80% of the infections caused by microorganisms are biofilm based. Biofilm architecture consists of structured and aggregated communities of bacteria encased in a self-secreted exopolymeric substance. Several studies have revealed that bacteria have developed resistance because of the prolonged treatment with conventional antibiotics possessing a broad-range efficacy via toxic or growth-inhibitory effects on target organisms rendering the traditional antibiotic treatment virtually ineffective. It has been found that bacteria living in the biofilm mode of growth are resistant to antibiotics up to 1000 times more than their planktonic counterparts. (Husain et al 2015)

      The presence of biofilms has been mostly seen in medical implants and urinary catheters. Various signalling events including two-component signalling, extra cytoplasmic function and quorum sensing are involved in the formation of biofilms. The presence of an extracellular polymeric matrix in biofilms makes it difficult for the antimicrobials to act on them and make the bacteria tolerant to antibiotics and other drugs. (Gupta et al 2015)

      Rationale for Using Anti-Quorum Sensing and Biofilm Disrupting Natural Compounds

      Acinetobacter frequently causes infections associated with medical devices, e.g. vascular catheters, cerebrospinal fluid shunts or Foleys catheter. Biofilm formation is a well-known pathogenic mechanism in such infections. The potential of Acinetobacter to form biofilm may explain its exceptional antibiotic resistance and survival in the hospital environment. This study concludes that there a positive correlation between biofilm formation and multiple drug resistance in A. baumannii. (Badave & Kulkarni 2015)

      Usage of antibiotics has caused pathogenic bacteria to become resistant and poses a global threat to public health. QS provides an alternative solution because by targeting bacterial communication the expression of the virulence phenotype is inhibited. (Tan et al 2013)

      Blocking quorum sensing pathways are viewed as viable anti-virulent therapy in association with traditional antimicrobial therapy. Anti-quorum sensing dietary phytochemicals with may prove to be a safe and viable choice as anti-virulent drug candidates. (Kumar et al 2015)

      Compounds that interfere with the QS system to attenuate bacterial pathogenicity are termed as anti-QS compounds. Such compounds neither kill the bacteria nor stop their growth and are less expected to develop resistance toward antibiotics. (Husain et al 2015)

      The likelihood of bacteria developing resistance to quorum sensing inhibitors is less probable than that observed with conventional antibiotics. (Kalia et al 2014)

      Natural products play a pivotal role for treating and preventing infectious diseases. Plant compounds usually target the bacterial QS system via three different ways, by either stopping the signaling molecules from being synthesized by the luxI encoded AHL synthase, by degrading the signaling molecules and/or by targeting the luxR signal receptor. (Koh et al 2013)

      Plant-derived anti-QS compounds such as oroidin, ursolic acid, naringenin, cinnamaldehyde, salicylic acid, methyl eugenol, and extracts from garlic and edible fruits, have shown antibiofilm properties against several pathogens. (Olivero-Verbel et al 2014)

      The following are summaries of 29 studies on anti quorum sensing and biofilm disrupting herbs, spices, foods and essential oils:

      Anti Quorum Sensing and Biofilm Disrupting Herbs, Spices, Foods and Essential Oils

      6-gingerol (a pungent oil of fresh ginger)
      Agaricus blazei Murill (edible mushroom)
      Ajoene (from Allium sativum)
      Areca catechu
      Armoracia rusticana (horseradish)
      Centella asiatica (gotu kola)
      Chamomile (Chamaemelum nobile)
      Cinnamon oil (Ceylon type)
      Citrus essential oil
      Clove essential oil
      Cranberry proanthocyanidins
      Colloidal silver
      Curcumin (from curcuma longa)
      Eucalyptus essential oil
      European Chestnut leaf (Castanea sativa)
      Garlic
      Geranium essential oil
      Gnetum gnemon (belinjo leaves)
      Imperata cylindrica
      Lavender essential oil
      Lemon essential oil
      Marjoram essential oil
      Menthol
      Nelumbo nucifera
      Nymphaea tetragona (water lily)
      Oxyresveratrol
      Panax notoginseng (root and flower)
      Phyllanthus amarus (chanca piedra)
      Piceatannol
      Piper betle (betle leaves)
      Piper nigrum (peppercorn), and Proanthocyanidin (from dried cranberry juice)
      Propolis
      Punica granatum
      Prunella vulgaris
      Prunus armeniaca
      Quercetin
      Resveratrol
      Rose essential oil
      Rosemary essential oil
      Utica dioica (Nettles)
      Wheat-bran 

      6-gingerol (a pungent oil of fresh ginger) reduced biofilm formation experimentally, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression. (Kim et al 2015)

      Agaricus blazei Murill (an edible mushroom) is known to induce protective immunomodulatory action against a variety of infectious diseases. In the present study we report potential anti-quorum sensing properties of A. blazei hot water extract. (Sokovic et al 2014)

      Armoracia rusticana (horseradish) stood out from a group of active crude extracts as highly active with respect to QSI activity against P. aeruginosa. Bioassay-guided fractionation and purification led to identification of 1-isothiocyanato-3-(methylsulfinyl) propane, commonly known as iberin, as an active QS inhibiting compound in horseradish. Real-time PCR (RT-PCR) and DNA microarray analysis of global gene expression revealed that iberin specifically and extremely effectively targets two of the major QS networks in P. aeruginosa, the LasIR and the RhlIR systems, and was found to downregulate QS-controlled rhamnolipid production in P. aeruginosa wild-type batch cultures. (Jakobsen et al 2012)

      Centella asiatica (gotu kola) – The anti-quorum sensing (QS) nature of Centella asiatica herb can be further exploited for the formulation of drugs targeting bacterial infections where pathogenicity is mediated through QS. (Vasavi et al 2014)

      Chamomile (Chamaemelum nobile) – The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound. (Kazemian et al 2015)

      Cinnamon oil (Ceylon type) – This work is the first to demonstrate that cinnamon oil can influence various quorum sensing (QS)-based phenomena in Pseudomonas aeruginosa PAO1, including biofilm formation. (Kalia et al 2015)

      Clove oil – The results of this study confirmed that the QS systems play an important role in the pathogenicity of P. aeruginosa infections. Consequently, compounds that attenuate QS may offer significant promise as potential therapeutic agents. These compounds provide alternative medicine for treating emerging bacterial infections without leading to antibiotic resistance as they do not pause selection pressure. Our study also revealed the anti-QS and biofilm inhibitory activity of clove oil against P. aeruginosa isolates. (Aboushleib et al 2015)

      Clove essential oil – Presence of anti-QS activity in clove oil and other essential oils has indicated new anti-infective activity. The identification of anti-QS phytoconstituents is needed to assess the mechanism of action against both C. violaceum and Ps. aeruginosa. (Khan et al 2009)

      Colloidal silver directly attenuates in vitro Staphylococcus aureus biofilms. (Goggin it al 2014)

      Cranberry proanthocyanidins (PACs) reduced P. aeruginosa swarming motility. Cranberry PACs significantly disrupted the biofilm formation of P. aeruginosa. Proteomics analysis revealed significantly different proteins expressed following PAC treatment. In addition, we found that PACs potentiated the antibiotic activity of gentamicin in an in vivo model of infection using G. mellonella. Results suggest that A-type proanthocyanidins may be a useful therapeutic against the biofilm-mediated infections caused by P. aeruginosa and should be further tested. ((Ulrey et al 2014)

      Cranberry proanthocyanidins – These findings indicate that cranberry proanthocyanidins (PACs) have excellent in vitro activity against C. albicans biofilm formation in artificial urine. We present preliminary evidence that cranberry PAC activity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation. (Rane et al 2014)

      Curcumin (Curcuma longa) – Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics. (Packiavathy et al 2014)

      Curcumin, from Curcuma longa, Ajoene from Allium sativum, Iberin from Armoracia rusticana attenuate P. aeruginosa virulence by downregulating the expression of QS genes. (Sarabhi et al 2013)

      European Chestnut leaf (Castanea sativa) extract – Here, we report the quorum sensing inhibitory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all Staphylococcus aureus accessory gene regulator (agr) alleles. (Quave et al 2015)

      Garlic (Allium sativum) is considered a rich source of many compounds, which shows antimicrobial effects. The ability of microorganisms to adhere to both biotic and abiotic surfaces and to form biofilm is responsible for a number of diseases of chronic nature, demonstrating extremely high resistance to antibiotics. Bacterial biofilms are complex communities of sessile microorganisms, embedded in an extracellular matrix and irreversibly attached to various surfaces. A. sativum L. extracts were efficient to inhibit biofilm structures and the concentration of each extract had a direct relation with the inhibitory effect. (Mohsenipour & Hassanshahian 2015)

      Marjoram essential oil (EO) and Lemon EO –  Marjoram EO inhibited Bacillus cereus, Pichia anomala, Pseudomonas putida and mixed-culture biofilm formation of Ps. putida and Escherichia coli and showed the best QS inhibitor effect on Chromobacterium violaceum. For B. cereus, all components showed better antibiofilm capacity than the parent EOs. Lemon EO inhibited E. coli and mixed-culture biofilms, and cinnamon was effective against the mixed forms. Scanning electron microscopy showed the loss of three-dimensional structures of biofilms. (Kerekes et al 2013)

      Menthol – Our data identified menthol as a novel broad spectrum QS inhibitor. (Husain et al 2015)

      Nymphaea tetragona (water lily) 50% methanol extract was demonstrated to have significant concentration-dependent inhibitory effects on quorum sensing-mediated virulence factors of bacteria with non-toxic properties, and could thus be a prospective quorum sensing inhibitor. (Hossain et al 2015)

      Phyllanthus amarus (chanca piedra) – Our data suggest that P. amarus could be useful for attenuating pathogens and hence, more local traditional herbs should be screened for its anti-quorum sensing properties as their active compounds may serve as promising anti-pathogenic drugs. ((Priya et al 2013)

      Piper nigrum (peppercorn), Piper betle (betle leaves) and Gnetum gnemon (belinjo leaves) – Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS) properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants have anti-QS ability. Interestingly, the hexane, chloroform and methanol extracts from P. betle showed the most potent anti-QS activity as judged by the bioassays. (Tan et al 2013)

      Proanthocyanidin – Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells. (Gupta et al 2011) Foods high in proanthocyanidins include: ground cinnamon, dried grape seeds, sorghum, unsweetened baking chocolate, red kidney beans, hazelnuts, pecans, chokeberries and cranberries.

      Propolis – Together, we present evidence that propolis contain compounds that suppress QS responses. In this regard, anti-pathogenic compounds from bee harvested propolis could be identified and isolated and thus will be valuable for the further development of therapeutics to disrupt QS signaling systems which regulate the virulome in many pathogenic bacteria. (Bulman et al 2011)

      Propolis – These results suggest that Tunisian propolis ethanol extract (EEP) is able to inhibit cancer cell proliferation, cariogenic bacteria and oral biofilms formation. It could have a promising role in the future medicine and nutrition when used as antibiotic or food additive. (Kouidhi et al 2010)

      Prunus armeniaca, Prunella vulgaris, Nelumbo nucifera, Panax notoginseng (root and flower), Punica granatum, Areca catechu, and Imperata cylindrica – Eight of the selected traditional Chinese medicine herbs (80%) yielded QS inhibitors: Prunus armeniaca, Prunella vulgaris, Nelumbo nucifera, Panax notoginseng (root and flower), Punica granatum, Areca catechu, and Imperata cylindrica. Compounds that interfere with QS are present in TCM herbs and these medicines may be a rich source of compounds to combat pathogenic bacteria and reduce the development of antibiotic resistance. (Koh & Tham 2011)

      Quercetin – This study suggests that quercetin can act as a competitive inhibitor for signaling compound towards LasR receptor pathway and can serve as a novel QS-based antibacterial/anti-biofilm drug to manage food-borne pathogens. (Gopu et al 2015)

      Resveratrol, piceatannol and oxyresveratrol – In the present study, quorum sensing inhibition activity of ten stilbenoids were tested using Chromobacterium violaceum CV026 as the bio-indicator strain and the structure-activity relationship was also investigated. Among them, resveratrol (1), piceatannol (2) and oxyresveratrol (3) showed potential anti-QS activities. (Sheng et al 2015)

      Rose, geranium, lavender and rosemary, eucalyptus and citrus essential oils – Of the tested essential oils, rose, geranium, lavender and rosemary essential oils were the most potent QS inhibitors. Eucalyptus and citrus essential oils moderately reduced pigment production by Chromobacterium violaceum CV026, whereas the chamomile, orange and juniper oils were ineffective. (Szabo et al 2010)

      Urtica dioica (Nettles) – The aim of this study was to assess the antibacterial and antifungal potential of some Romanian medicinal plants, arnica-–Arnica montana, wormwood–Artemisia absinthium and nettle–Urtica dioica. In order to perform this antimicrobial screening, we obtained the vegetal extracts and we tested them on a series of Gram-positive and Gram-negative bacteria, and also against two fungal strains. The vegetal extracts showed antimicrobial activity preferentially directed against the planktonic fungal and bacterial growth, while the effect against biofilm formation and development was demonstrated only against S. aureus and C. albicans. Our in vitro assays indicate that the studied plant extracts are a significant source of natural alternatives to antimicrobial therapy, thus avoiding antibiotic therapy, the use of which has become excessive in recent years. (Stanciuc et al 2011)

      Wheat-bran (WB) – The soluble extract of WB at 0.5% showed anti-biofilm activity, inhibiting biofilm formation and also destroying it. Similarly, the > 300 kDa fraction from WB had significant anti-biofilm activity in both in vitro assays. The WB also showed a potential to interfere with bacterial QS systems, as it was demonstrated to contain certain lactonase activity able to reduce AHL concentration in the medium. The present study reveals two additional beneficial properties of WB extract never explored before, which may be related to the presence of defence compounds in the plant extract able to interfere with microbial biofilms and also QS systems. (Gonzalez-Ortiz et al 2014)

      *****

      Compassionate Acupuncture and Healing Arts, providing craniosacral acupuncture, herbal and nutritional medicine in Durham, North Carolina. Phone number 919-475-1005

       

      Posted in acute conditions, antibiotic resistance, antimicrobial actions, bacterial diseases, bacterial resistance, biofilm formation, botanical medicine, chronic conditions, dietary recommendations, foods, herbal medicine, nutritional medicine, quorum sensing, Traditional Chinese Medicine | Tagged , , , | Leave a comment