Gestational diabetes and metformin-Is that the best that medical thinking has to offer?

Gestational diabetes or elevated blood sugar is often treated with metformin to improve blood sugar levels and considered the standard approach to treating gestational diabetes. The research suggests that it has little negative effects on the pregnant mother. However, does significant risks to both mother and baby if the incidence of premature birth count? Here are a few aspects to consider regarding the use of metformin to control blood sugar during pregnancy.

A study of patients receiving a dose of metformin, combination of Clomiphene citrate (CC) and metformin both faired better than CC alone for the induction of ovulation (Neveu, Granger, St-Michel, & Lavoie, 2007).  As the combined group showed no benefit compared to metformin alone, one might consider that metformin alone may be considered for the positive effects.

In another study metformin and diet interventions showed a significant outcome compared to non-metformin-diet interventions. The metformin diet showed a reduction of 14 adverse events in a group of 76 expectant mothers, compared to the non-treated group of 36 adverse events out of 76 pregnancies (Glueck et al., 2013).

Thatcher and Jackson (Thatcher & Jackson, 2006) compared pregnancies of 188 women. 61 experienced miscarriages and 11 of those had stopped taking metformin, suggesting other abnormalities beyond metformin’s actions. 81% of women with pregnancies before metformin, 67% had prior miscarriages. 37% of these also miscarried again. Whilst metformin appeared to show minimal effects to mother and foetus 22% were born prematurely.

Whilst metformin has shown favourable outcomes in PCOS states, questions around pertinent biological mechanisms should warrant further discussion. It’s well known that two key endocrine actions may be compromised during the failure to achieve full gestation. Estrogen induces hypoxia in the uterus (Peat, 1997) and failure to produce adequate progesterone to counter the effects of estrogen may be implicated in the commonly fragile time around weeks 9-10 of pregnancy and incidence of miscarriage.

A concern of metformin are its affect transplacentally. Metformin appears to influence testicular size in males and affects sertoli cells. In females it may also lead to decreased androgen synthesis. Birth weight percentile is also significantly lower in pregnancies treated with metformin (Bertoldo, Faure, Dupont, & Froment, 2014)I Metformin has generally appeared safe in expecting mothers but considerable concern should be made regarding its long term effects to offspring and development most notably to reproductive tissues.

Hypothyroidism is a key factor in maintenance of pregnancy and alongside progesterone, thyroid hormone deficiency can be implicated in poor cellular energetics, production of adenosine tri phosphate (ATP) and blood sugar regulation. There remains much debate about the issue of subclinical hypothyroidism, values and when to treat and perhaps metformin’s role despite showing some promises may be treating a symptom related to insulin sensitivity. Failure

So perhaps these questions might be more pertinent before prescribing an agent that shows potentially negative effects to the fetus?

  1. What is the nutrition of the mother, is it enough and does it contain enough nutrients to enhance/maintain adequate progesterone/thyroid production?
  2. Is estrogen increasing at a rate that suppresses progesterone/thyroid levels and persistently decreases insulin sensitivity?
  3. Is there enough carbohydrate in the diet to ensure that carbohydrate is effectively utilised instead of persistent conversion of fats, increasing overall stress to both mother and fetus?
  4. Are the values of hypothyroidism and the identification of subclinical/functional hypothyroid factors appropriate?
  5. Is gestational diabetes a reflection of the above points?

The use of metformin, without questioning these mechanisms, remains at best a reduced treatment that fails to address a range of biological interactions and function.


Bertoldo, M. J., Faure, M., Dupont, J., & Froment, P. (2014). Impact of metformin on reproductive tissues: an overview from gametogenesis to gestation. Annals of Translational Medicine2(6), 55.

Glueck, C. J., Goldenberg, N., Pranikoff, J., Khan, Z., Padda, J., & Wang, P. (2013). Effects of metformin-diet intervention before and throughout pregnancy on obstetric and neonatal outcomes in patients with polycystic ovary syndrome. Current Medical Research and Opinion29(1), 55–62.

Neveu, N., Granger, L., St-Michel, P., & Lavoie, H. B. (2007). Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertility and Sterility87(1), 113–120.

Peat, R. (1997). From PMS to Menopause: Female Hormones in context.

Thatcher, S. S., & Jackson, E. M. (2006). Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertility and Sterility85(4), 1002–1009.

Osteoporosis- could your exercise, nutrition and medical advice be better?

Osteoporosis and bone health, like many other aspects of optimal biology is a product of an organisms inputs and reactions to environmental stimulus. Osteoporosis is a condition like others, where prevention is often easier than the cure but perhaps the cure has been overcomplicated? Osteoporosis is a multifactorial musculoskeletal disease that is usually associated with the ageing process, decreased bone mineral density (BMD) and its tendency to fracture easily.      

It’s clear that a number of factors that can be maintained throughout life to reduce the incidence of Osteoporosis in both men and women. Before we review those and compare with current guidelines, here’s some background info on the subject.

Primary Osteoporosis is the age related decline in men at around 70 and suggested as being a postmenopausal state, induced through the decreased production of estrogen in females. This last point is accepted in medical literature as the main cause of osteoporosis in females but may be severely flawed (more on this point later).

Secondary osteoporosis can be related to the following factors

Hypogonadism – testosterone/estrogen deficiency
Endocrine disease – Cushing’s syndrome, acromegaly, thyrotoxicosis, Addison’s disease and hyperparathyroidism
Dietary or assimilation deficiencies of calcium, vitamin K, vitamin D and other nutrients
Inflammation-rheumatoid arthritis, systemic lupus and ankylosing spondylitis
Neoplasms- Myleoma, lymphoma and leukaemia
Reduced physical activity
Medical drugs – corticosteroids, antiretroviral, antipsychotic, chemotherapy, hormone therapy, nicotine and excessive alcohol
Family history/genetics

The financial burden from osteoporosis generally, will increase from 98 Million Euros to 121 billion with proportional increases of 27.5 million to approximately 34 million people between the years 2010 to 2025 (Hernlund et al., 2013). Despite these huge burdens there appears to be a lack of well-designed educational programs that are geared at prevention of osteoporosis through non-pharmacological means.

The supplementation of vitamin D and calcium are well documented in osteoporosis strategies but a strategy to avoid these states are diets containing adequate calcium, vitamin A, K, magnesium (and others) adequate sunlight and moderate exercise.

Ok, so there’s a problem, it’s big business and there’s a lot of great info on how to avoid it right? Well no and here are the major points why I believe its not.


 Dual energy X-ray absorptiometry (DEXA) is the recommended choice for osteoporosis diagnosis, serum calcium, phosphate, creatinine (with GFR) alkaline phosphatase, liver function, 25 OHD, total testosterone, estrogen CBC and 24 urinary calcium excretion are recommended for the interpretation of secondary causes of osteoporosis (Watts et al., 2012).


Estrogen loss is touted as the most significant factor in decreasing BMD yet it’s action only retards resorption, or the removal of calcium from bone. Estrogen tends to inhibit the action of osteoclasts which ultimately reduce BMD. It’s the main reason the introduction of hormone replacement therapy (HRT) was considered as the primary treatment until its long-term use was found to induce clotting and cancer in women. So estrogen does not reverse Osteoporosis, it prevents further bone loss.

A variety of studies have suggested little influence of testosterone in males on BMD and that low estradiol levels combined with elevated sex hormone binding globulin appear to increase the loss of BMD (Cauley et al., 2010). A point worth noting from the correlation associated with higher estradiol levels and decreased BMD loss is that all participants in the study were recorded as having increased weight and BMD, which may influence skeletal modelling due to increased bone-loading parameters. Perhaps too much emphasis has been given to the suggestion that estrogen and its primary role of tissue proliferation amongst others, which should follow the course of age related decline?

Progesterone on the other hand has been shown to be a bone trophic or building factor that increases mineralisation of BMD, via osteoblasts (Prior, 1990). Stress increases cortisol and decreases progesterone binding at the receptor, with a preference for the glucocorticoid. Ray Peat (1997) points out that cortisol causes bone loss and its widely accepted that progesterone has an “antiglucocorticoid” action, it is reasonable to think that progesterone should protect against bone loss, and that it is a progesterone deficiency after menopause which is a major factor in the development of osteoporosis.

Thyrotoxicosis has been suggested as a mechanism of bone resorption but this appears inaccurate-  Ray Peat does a much better job at explaining this.

Medical treatment

Bisphosphonates are the first line medical treatment for treating osteoporosis and show modest changes to hip and vertebral BMD over 3 years. There use may come at a risk. Gastro intestinal side effects are well documented and in some the increase of osteonecrosis of the jaw has been observed. In some, the long-term use has been shown not only to increase the rate of fragility fracture but also to inhibit the healing process. It should be noted that adequate calcium and vitamin D in the diet are essential for bisphosphonate effectiveness


 There tend to be two well-known stances to the fitness industries approach to nutrition. One, the transformation approach, where limiting of nutrients, particularly dairy and carbohydrates and intermittent fasting are the norm. Another, the holistic warrior whose consumption of chia seeds and all things green, raw and limiting of dairy and sugar again,  may be a factor into lowering BMD in later life. Calcium is an essential nutrient for bone health and dairy is indeed a great source of calcium. Here’s an old blog on the subject.

 It’s clear that adequate vitamin D is a nutrient that is important in BMD maintenance. It regulates calcium levels, decreases the production of parathyroid hormone, which is a potent resorption factor of skeletal calcium when calcium or vitamin D are low. Here are the main points that relate to diet.

  • Vitamin D in isolation and particularly high doses increases fracture rates (Janssen, Samson, & Verhaar, 2002)
  • Unless vitamin D is accompanied by adequate calcium, BMD can decrease further.
  • Vitamin K2 can prevent the calcification of soft tissues and help improve blood calcium levels (Masterjohn, 2007)
  • High meat and diets high in pulses and beans can have a negative effect on calcium levels due to their high phosphate levels.
  • Unless you assess other key nutrients like magnesium and the factors discussed above
  • Low diary intake can be associated with poor bone health.
  • The low carbohydrate, raw green and seed eating diet suggested by holistic health practitioners may contribute to lower BMD.


Regular exercise has been touted as a significant factor in maintaining muscle mass and increasing BMD. But is the type of exercise that people are doing, increasingly in their younger years, contributing to better or worse outcomes to BMD. For bone to form adequate carbon dioxide (CO2 ) is essential. Some exercise regimes are so challenging, they contribute to excess levels of metabolic acidosis (lactic acid) and passing of CO2 from the body (worth noting that sugar consumption can also help to increase CO2 production) . Perhaps for exercise to be effective it should be light to moderate, with adequate rest periods that don’t mean that the participant is lying in a pool their sweat and vomit.

Walking, strength training with adequate rest, yoga, Pilates and other modes of moderate exercise appear most suitable for modest improvements to bone health but the diet and hormone factors are key.

It’s clear that osteoporosis is in the rise but it can be reversed. But instead of heading advice like cutting out dairy, eating lots of uncooked vegetables and training to complete exhaustion. There are more suitable mechanisms for improving bone health


Cauley, J. A., Ewing, S. K., Taylor, B. C., Fink, H. A., Ensrud, K. E., Bauer, D. C., … Orwoll, E. S. (2010). Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density–the osteoporotic fractures in men study. The Journal of Clinical Endocrinology and Metabolism, 95(9), 4314–23.

Hernlund, E., Svedbom, a, Ivergård, M., Compston, J., Cooper, C., Stenmark, J., … Kanis, J. a. (2013). Osteoporosis in the European Union: medical management, epidemiology and economic burden. Archives of Osteoporosis, 8(1–2), 136.

Janssen, H. C. J. P., Samson, M. M., & Verhaar, H. J. J. (2002). Vitamin D deficiency, muscle function, and falls in elderly people. The American Journal of Clinical Nutrition, 75(4), 611–5. Retrieved from

Masterjohn, C. (2007). Vitamin D toxicity redefined: Vitamin K and the molecular mechanism. Medical Hypotheses, 68(5), 1026–1034.

Peat, R. (1999). Thyroid Therapies, Confusion and Fraud. Retrieved from

Prior, J. C. (1990). Progesterone as a bone-trophic hormone. Endocrine Reviews, 11(2), 386–398.

Watts, N. B., Adler, R. A., Bilezikian, J. P., Drake, M. T., Eastell, R., Orwoll, E. S., & Finkelstein, J. S. (2012). Osteoporosis in men: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 97(6), 1802–1822.