Anthropometry is a method to assess malnutrition, which considers various aspects of human growth and well-being, such as stunting, wasting, underweight, overweight, and obesity. However, in our view, muscle wasting at the daily microscopic level is the root cause of all forms of malnutrition. This chronic wasting can lead to stunting at a young age and overweight/obesity in adults. The underlying cause of muscle wasting is still not fully understood. While some researchers have attributed it to insufficient dietary protein10 or poor quality protein intake11, we suggest that a cascade of events triggered by VDD (such as muscle damage, protein malabsorption, endothelial dysfunction, protein loss through the kidney, gut microbiota dysbiosis, and malabsorption syndrome) is the primary cause (Suppl: Annexure 2). Therefore, addressing vitamin D levels and supplementation is crucial for preventing anthropometric failure (S:1.1). Although VDD contributes to muscle wasting (S:1.2), secondary micronutrient deficiencies induced by VDD exacerbate the condition (Fig. 2, Table 2).
Studies have typically focused on examining a single parameter and attempting to establish a cause-effect relationship with a disease. For example, zinc has been identified as a key factor in stunting by some researchers12, while others have linked stunting to anaemia13, vitamin B1214, folate15 and Vit-D16. However, we have compiled evidence that suggests a central role for both Vit-D and Boron deficiencies in malnutrition statuses such as anaemia (Fig. 1B), wasting, stunting (S:1.3), and obesity (S:1.4). These twin deficiencies (vitamin D and Boron) affect mineral (S:1.5), vitamin (S:1.6) and hormone (S:1.7) homeostasis across all age groups, with pregnant mothers being particularly vulnerable (S:1.8). Interestingly, both nutrients depend on sunlight, making them part of the "CNCOTF" group. It is worth noting that the impact of other deficiencies is usually secondary to these twin deficiencies.
Interventions
The triple burden of malnutrition presents a complex challenge that requires a multidisciplinary approach (Fig. 3) to address the rhetoric of ‘Hunger Index’ (S:2.1). While Vitamin D supplements have been available for some time, their fortification (S:2.2) and supplementation (S:2.3) are still in the early stages due to insufficient guidelines and fear of toxicity (S:2.4). It is hoped that this paper will provide a useful guide to these bodies. Conversely, research on boron has been largely overlooked (S:2.5), and while supplements are available, their synthetic/inorganic nature and doubts about their bioavailability and toxicity limit their effectiveness. Furthermore, naturally occurring boron (NOB), which is better absorbed and utilised by the body, is increasingly scarce in food and water sources due to changes in agriculture and drinking water sources. Therefore, interventions aimed at improving NOB access and utilisation should be considered.
The knowledge and experience with vitamin D and boron in sports nutrition are not being utilized to treat malnutrition in the general population, despite being widely available. China has demonstrated leadership in addressing these challenges (S:2.6.) through various initiatives in the agriculture sector (S:2.6.1.), including the production of mushrooms (a vegan source of vitamin D2) and lichens (a vegan source of vitamin D3). They have also made strides in veterinary medicine (S:2.6.2.) and related fields, such as biofortification, fisheries, and the sheep wool industry, which is now the largest exporter of vitamin D raw material globally. We believe that India can follow a similar path towards overcoming malnutrition through a “One Health approach” and “Health in all Policies” concepts that strengthen health policies (S:2.7.). This approach will not only prevent policy paralysis caused by data-driven research but also provide practical recommendations that can be successfully implemented.
In our opinion, a simple and cost-effective approach to address vitamin D and boron deficiencies in humans could be to enrich mushrooms with boron through spraying boric acid solutions during the growing process. However, the cultural acceptance of this strategy and the cost associated with producing mushrooms in India may pose an implementation challenge. By sun-drying or irradiating these mushrooms with UVB, the concentration of bioavailable vitamin D2 can be significantly increased. This way, a single food source that is acceptable to the vegetarian population can address both vitamin D and boron deficiencies.
Arguments
Numerous researchers have advocated for the consumption of iron and zinc in the form of supplements and fortification, and guidelines have been established accordingly. However, the outcomes have not been satisfactory, and we strongly urge a re-evaluation of these practices (S:1.5.1 and S:1.5.2.) with a thorough investigation into their effects and potential side effects. As research suggests that inorganic supplements may lead to detrimental health effects through gut microbe dysbiosis (S:3.1.), we propose that greater attention be paid to the role of vitamin D and boron in maintaining homeostasis.
There is ample evidence to suggest that the dysbiosis of gut microbiota and gut inflammation are among the significant side effects of fortification and supplementation with iron and zinc, as documented in various publications17–19. Furthermore, when vitamin D is inadequate, an existing deficiency can exacerbate these side effects, as highlighted in "The Dark Side of Supplementation"20. We believe that VDD and BD have devastating health effects in the Indian population and may be responsible for the inadequate success of existing nutrition policies.
India has a high morbidity and mortality rate from vector-borne diseases, and VDD has been repeatedly associated with the severity and recovery from such communicable diseases (S:3.2.). India also has a significant burden of non-communicable (S:3.3.) and fungal diseases (S:3.4.), both of which have been linked to vitamin D levels in several studies. Eradicating tuberculosis from India is a significant challenge, and it cannot be achieved without addressing boron and vitamin D deficiency (S:3.5.).
While animal studies on individual nutrients show positive results, translating these results to human studies has been difficult. This could be because animals are fed a complete diet containing adequate amounts of bioavailable vitamin D and boron. However, in the Indian context, a significant percentage of the population has VDD (less than 30 ng/ml)21 irrespective of age or gender and Boron is unavailable in the soil. This leads to negative outcomes in translational studies and in the implementation of strategies based on animal studies.
Vdd And Policy Hurdles... The Way Forward
Making small changes can have a significant cumulative effect, and it is achievable. Therefore, we will discuss below the challenges and potential solutions for eliminating malnutrition in India through the adequate supply of Vit-D and boron. However, we must first recognize and address the overlooked regional and cultural factors contributing to malnutrition, as well as the challenges in policy implementation, before developing guidelines.
India is currently facing a pandemic of VDD, which is known to significantly impact the severity, course, and prognosis of diseases. Non-communicable diseases such as anaemia and hypothyroidism (Fig. 1B) can be costly in terms of morbidity. Treating infections can also put a strain on a country's economy but investing in nutrition can help alleviate this issue. Over the years, animal husbandry has been developed to increase productivity and maintain animal health during production cycles.
Our analysis suggests that Vitamin D deficiency is a silent epidemic, which becomes more apparent when different cut-off levels are applied. However, researchers and policymakers in various countries have chosen lower cut-off levels. Positive effects on non-skeletal tissues have been observed at higher Vitamin D levels (above 30–40 ng/ml). In India, the CNNS report indicates a Vitamin D deficiency in the population when a cut-off value below 12 ng/ml is used (23.5%). However, when the cut-off level is set at 30 ng/ml, the percentage of deficiency increases significantly by 3.87-fold (90.9%), leaving a large proportion of the population at risk as a “shadow effect".
VDD is commonly linked to bone mineralization issues, such as osteomalacia, with severe deficiency defined as 12.5 ng/ml and moderate deficiency as 20 ng/ml. However, the non-skeletal effects of VDD, which occur when Vit D levels remain below 30–37 ng/ml, are often disregarded in the definition. Notably, a study on bone biopsies has shown that osteoid formation occurs at Vit D levels below 30 ng/ml22, among other pieces of evidence. Several factors causing VDD in India include regional air pollution, soils lacking organic carbon, abandonment of traditional cultural practices (unpublished data), and an unwarranted fear of toxicity. Interestingly, the uptake of Vit-D and boron is interdependent. Nevertheless, the conflict (‘tug of war’) between the fear of toxicity and false sufficiency (Fig. 4) has resulted in insufficient attention to revising the reference interval for normal levels of boron and Vit-D in the blood. Therefore, the Recommended Dietary Allowance (RDA) and the supplementation system for Vit-D and boron need to be re-examined. An interdisciplinary approach is necessary to collect the information needed to formulate a sustainable policy.
Vitamin D and boron both directly affect endocrine functions, particularly growth hormones and thyroid hormones. Having adequate intake of these nutrients may have a positive impact on growth hormone levels and correct thyroxine deficiency in girls of different age groups, as well as non-breastfeeding postpartum women23, through the influence of VDR on thyroid-binding protein. Studies have shown that vitamin D supplementation can affect thyroid autoimmunity, various thyroiditis, Graves' disease, and thyroid cancer24. However, we believe that vitamin D supplementation alone, without considering boron levels, may not be sufficient to provide substantial evidence for alleviating thyroid disease. In recent times, the veterinary industry has adopted a trend of keeping livestock and poultry outdoors (free-range) to address these issues. Similarly, promoting sun exposure activities in open offices and schools can ensure an adequate supply of Vit-D and boron.
Although the effects of VDD and boron on hyperphagia, neuronal responses to high-energy food, and inflammation are significant, these can lead to metabolic disturbances in the long term and should not be overlooked. Pre-pregnancy interventions in the form of Vit D supplements can help prevent DNA changes, improve placental growth, and blood flow, and affect anthropometry. Vitamin D supplementation during pregnancy can also play a role in preventing “malignant hypertension” (due to insufficient growth of nephrons), obesity in children aged six and above, and “iatrogenic infantile hyperphosphatemia” in the F1 generation. It is surprising to note from the evidence that the detrimental outcomes of VDD in pregnant women can endure for two consecutive generations and result in dual defect (pre & postnatal) in ALP levels among children born to VDD mothers (S:1:8).
Numerous attempts have been made to increase the levels of Vit D, but their efficacy has been limited. This may be attributed to various factors, such as insufficient awareness among the population, inadequate understanding of the causes of Vit D deficiency, apprehensions related to food fortification by the food industry, and obstacles in implementation due to diverse cultural and religious practices. It is disconcerting that the proportion of individuals experiencing deficiency symptoms has not declined, and the prevalence of VDD in India remains high (70–100%), caused by factors such as lack of light exposure due to high-rise buildings, sedentary lifestyle, and skin colour issues25. Other contributing factors include poor dietary habits, misinformation, and inadequate fortification, among others.
Despite numerous calls from researchers to raise cut-offs and safety limits for several decades26, these recommendations have been disregarded27, which raises questions about missed evidence in current policies. Several countries have already revised and updated their Vit D policies (S:2.7.2), and some have developed strategies to reduce the costs of dietary supplements28. On the other hand, some countries exceed the Recommended Dietary Allowance (RDA) for Vitamin D intake29, while others set lower RDAs and very low cut-off levels for Vitamin D deficiency screening. This issue requires urgent attention. Strategies to improve anthropometry have been implemented in China (S:2.9) and the Netherlands, including increased consumption of milk and dried mushrooms, fortification of vertical chain of food items, promotion of mushroom (S:2.9.1) and lichen (S:2.9.2) cultivation, and production of sheep wool oil for Vitamin D3.
Several studies have yielded "inconclusive results", possibly due to a lack of understanding about the effect of boron as a substitute or its synergistic effect on Vit-D, as well as the absence of consensus on the existing cut-off values for VDD and BD in humans. Through a review of the literature on boron in various fields, including agriculture, veterinary medicine, meteorology, horticulture, irrigation, and physics, we can better understand the factors of BD and its effects on living organisms, from microbes to animals. This has elucidated the overlooked pathways involved in the complexity of vitamin D deficiency in countries such as India, where a significant portion of the population is deficient despite adequate sunlight exposure.
To overcome implementation problems, it appears that a revision of the current policy is necessary. While food fortification can help alleviate deficiencies, it is plagued with issues such as dispensing/manufacturing errors and inconsistencies in control mechanisms of fortified products. However, “natural biofortification”, aided by veterinary science, may offer a safer alternative that reduces the associated risks.
Finally, Boron and vitamin D work together like a team (‘toggle switch’), complementing and enhancing (synergistic) each other in various ways to maintain balance in our body's functioning. They are like a pair of strong oxen pulling a cart (Fig. 5A) efficiently (‘ox-wagon/bullock-cart analogy’), but if one of them is weak, it can cause stress on the other and decrease their performance over time. The importance of both nutrients in achieving optimal health has been overlooked, especially in the Indian population where dual deficiencies are prevalent and can lead to health issues and growth problems. Unfortunately, vitamin D levels are often measured without taking into account boron levels, which can lead to a misunderstanding of their correlation with certain diseases or disorders.