1. Muscles starve in the absence of vitamin D, study of mice finds

The study examined the molecular nature of muscle dysfunction in mice, in the absence of vitamin D

Skeletal muscles normally brim with energy, yet they starve in the absence of Vitamin D, says recent research led by Aneeshkumar A. G. of National Institute of Immunology, New Delhi. This research demonstrates that glycogen stored in the skeletal muscles is not converted into a usable form of energy without Vitamin D.

Usually, the glucose absorbed from the food is converted into glycogen and stored in the skeletal muscle. This stored energy reserve is used by muscles to produce energy after the food consumed is digested. However, in the absence of vitamin D, the skeletal muscle is starved of energy, decreasing muscle mass.

Muscle wasting

Vitamin D deficiency is often associated with rickets. In rickets, the bone tissue does not correctly mineralise calcium and phosphorus, leading to softening of bones resulting in skeletal deformities. However, we are becoming aware that vitamin D works more as a hormone than and is involved in a host of biochemical reactions. It is key to maintaining metabolic functions, immune system, bone health and plays a crucial role in depression, mood swings, anxiety and sleep quality.

As part of the normal metabolic process, proteins produced in our body degrade, and in due course, new proteins are made to replace them. Usually, when the protein degradation exceeds protein synthesis, skeletal muscle atrophy or simply a decrease in muscle mass occurs.

“We wanted to find out the molecular nature of muscle dysfunction in the absence of vitamin D. We started with the hypothesis that the root cause is metabolic dysfunction. We used a mouse model which does not have a vitamin D receptor:[VDR] a protein that binds to vitamin D and switches several genes on or off to test our hypotheses,” says Dr. Aneeshkumar.

Hungry cells

Typically, the protein synthesis is high when the digestion of the food is taking place and is slower during the post-absorptive state when the digestion is completed. “In order to examine if the protein degradation and subsequent muscle wasting occur primarily during the absorptive or post-absorptive phase, we compared the protein synthesis during both the phases. In control mice, the levels were as expected. Nevertheless, in mice lacking VDR after the weaning stage of growth, the protein synthesis was impaired during the post-absorptive stage,” explains Dr. Aneeshkumar, and adds, “without the vitamin D receptor there was a general increase in protein degradation and a decrease in post-absorptive protein synthesis.”

Initially, scientists suspected that the absence of VDR is preventing the synthesis of glycogen from the food. “We checked whether the energy deprivation in skeletal muscles is associated with differences in glycogen levels,” says Dr. Aneeshkumar. To their surprise, VDR knockout mice had higher glycogen levels than the control ones. “We found that the glycogen synthase, the key enzyme that converts glucose into glycogen, was having a field day without the inhibitory enzymes active”. More and more glycogen was being produced and stored in the skeletal muscle.

Nevertheless, the glycogen phosphorylase, an enzyme that converts glycogen to glucose when energy is needed, was significantly lower. “As a result, while muscle continued to make glycogen, none of it could be converted back to glucose resulting in energy deficiency,” explains Dr. Aneeshkumar. Even with abundant glycogen present, the skeletal muscle could not extract the energy in the absence of vitamin D.

“From this research, we think we have found the molecular mechanism by which the vitamin D deficiency leads to muscle wasting. Without vitamin D, glycogen storage cannot be utilised for glucose production. When the glycogen storage does not give energy, particularly in a post-absorb state, the skeletal muscle draws more glucose from the blood. This leads to a systemic energy shortage. When there is systemic lack of energy, like during hunger, the protein degradation in muscle is triggered leading to muscle wasting,” explains Dr. Aneeshkumar. “Although our study is in mice, we think this mechanism is broadly applicable in humans as well,” he said.

Vitamin D

• Vitamin D is a fat-soluble vitamin which is naturally present in very few foods like fatty fish, and fish liver oils, beef liver, cheese, and egg yolks.
• It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis.
  
  
  • The sunlight triggers a chemical reaction to a cholesterol-based molecule, and converts it into calcidiol in the liver and into calcitriol in the kidney.
  • These molecules technically called 25-OHD are physiologically active.

• Role:
  
  
  • Vitamin D maintains adequate calcium and phosphate concentrations in blood. It prevents weakening of bones.
  • Vitamin D has other roles in the body, including cell growth, neuromuscular and immune function, and reduction of inflammation.
• Required Amount
  
  
  • The level of 25-OHD in the range 30-100 ng/ml is thought to be sufficient for a healthy body; levels between 21-29 ng/ml are considered insufficient, and levels below 20 ng/ml mean the individual is deficient in the vitamin.
• Effects of Deficiency:
  
  
  • Rickets in children and osteomalacia (softening of bones) in adults.
  • Bones can become thin, brittle, or misshapen (Effects of deficiency).
  • Vitamin D deficiency can cause rickets in children and osteomalacia in adults.
  • Bones can become thin, brittle, or misshapen (osteoporosis) Vitamin D.

Vitamin A (Retinol)

Vitamin A is required in the production of rhodopsin, the visual pigment used in low light levels. This is why eating foods rich in vitamin A is often said to allow an individual to see in the dark, although the effect they have on one’s vision is negligible.

Vitamin A is also essential for the correct functioning of epithelial cells. In vitamin A deficiency, mucus-secreting cells are replaced by keratin producing cells, leading to xerosis.

Vitamin B (Thiamine)

Vitamine B (Thiamine) deficiency produces beriberi, Wernicke-Korsakoff syndrome, and optic neuropathy.

Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder are dry beriberi, wet beriberi, and infantile beriberi. Dry beriberi is characterized principally by muscular dysfunctions, while Wet beriberi is associated with mental confusion, muscular atrophy, edema. Infantile beriberi occurs in infants breast-fed by thiamin-deficient mothers.

Vitamin C (Ascorbic Acid)

Ascorbic acid is found in plants and animals where it is produced from glucose.  Humans are unable to make ascorbic acid. This Vitamin is also an antioxidant and antioxidant properties of ascorbic acid are only a small part of its effective vitamin activity.

Vitamin D (Calciferol)

Calciferol is not actually an essential dietary vitamin in the strict sense, as it can be synthesized in adequate amounts by most mammals exposed to sunlight.

Vitamin E (Tocopherol)

Vitamin E is a series of organic compounds consisting of various methylated phenols. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was given the name “tocopherol” or birth carrying vitamin.

There are eight forms of Vitamin E. In general, food sources with the highest concentrations of vitamin E are vegetable oils, followed by nuts and seeds including whole grains. The highest sources of Tocoferol are Wheat germ oil (215.4 mg), Sunflower oil (55.8 mg), Almond oil (39.2 mg), Sunflower seed (35.17 mg) and Almond (26.2 mg).

Vitamin E deficiency causes neurological problems due to poor nerve conduction. It has been linked to Age-related macular degeneration (AMD), Alzheimer’s disease. Vitamin E is widely used as an inexpensive antioxidant in cosmetics and foods. Vitamin E containing products are commonly used in the belief that vitamin E is good for the skin; many cosmetics include it. The function is mainly associated with Vitamin E being a powerful antioxidant. It also plays important role in skin health.

Vitamin K1 (Phylloquinone)

Phylloquinone is an electron acceptor during photosynthesis. Its best-known function in animals is as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX, and X by the liver.  It found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis. It may be thought of as the “plant form” of vitamin K.

Vitamin K2 (menaquinone)

It may be thought of as the “animal form” of vitamin K. Bacteria in the colon (large intestine) can also convert K1 into vitamin K2.

Vitamin B5 (Pantothenic acid)

Animals require pantothenic acid to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats.

Vitamin B7 (Biotin)

Biotin is a coenzyme for carboxylase enzymes, involved in the synthesis of fatty acids, isoleucine, and valine, and in gluconeogenesis. It is also known as Vitamin H. Biotin deficiency is rare and mild, and can be addressed with supplementation.

It is caused by the consumption of raw egg whites (two or more daily for several months) due the avidin they contain, a protein which binds extremely strongly with biotin, making it unavailable. The defecinecy causes hairloss and skin problems mainly.

Vitamin B6 (Pyridoxine)

Pyridoxine assists in the balancing of sodium and potassium as well as promoting red blood cell production. It is linked to cardiovascular health by decreasing the formation of homocysteine.

Pyridoxine may help balance hormonal changes in women and aid the immune system. Lack of pyridoxine may cause anemia, nerve damage, seizures, skin problems, and sores in the mouth.

Vitamin B3 (Niacin)

It is also known as nicotinic acid and vitamin PP. Niacin is used to increase levels of HDL in the blood and has been found to modestly decrease the risk of cardiovascular events in a number of controlled human trials.

Vitamin B9 (Folic acid)

Also known as Vitamin M and Folate, Vitamin B9 is essential to numerous bodily functions. The human body needs folate in DNA synthesis and repair. It is also important in cell division and growth during pregnancy. Children and adults both require folic acid to produce healthy red blood cells and prevent anaemia. Deficiency can result in many health problems, the most notable one being neural tube defects in developing embryos.

2. Why is India challenging WTO verdict on sugar?

When did Australia, Brazil and Guatemala file a complaint and what are the rules?

The story so far: India this week filed an appeal with the Appellate Body of the World Trade Organization (WTO) disputing a verdict by the WTO’s dispute settlement panel last month on sugar subsidies. The WTO’s dispute settlement panel had ruled that India, by subsidising sugar producers, was breaking rules framed under the General Agreement on Tariffs and Trade (GATT) which govern international trade.

What is it?

In 2019, Australia, Brazil, and Guatemala complained against India at the WTO arguing that subsidies offered by the Indian government to sugar producers were against the rules governing international trade. They argued that these subsidies, which include both domestic subsidies as well as export subsidies, exceed the limits imposed by WTO trade rules. According to WTO rules, subsidies cannot exceed 10% of the total value of sugar production. These countries believe that subsidies offered by India have led to increased production of sugar and caused the price of sugar to drop significantly in the global market. After two years, the WTO ruled in December that India’s sugar policy was favouring domestic producers through subsidies to the detriment of foreign producers. The panel recommended that India withdraws its alleged prohibited subsidies under the Production Assistance, the Buffer Stock, and the Marketing and Transportation Schemes within 120 days from the adoption of this report. India has stated that the WTO’s dispute panel ruling has made certain “erroneous” findings about domestic schemes to support sugarcane producers and exports and the findings of the panel are completely “unacceptable” to it.

India is the second-largest sugar producer in the world after Brazil and it is estimated that more than 5 crore people depend on the cultivation of sugarcane alone for their livelihood.

What is India’s stand?

India has argued at the WTO that it does not offer direct subsidies to sugarcane farmers and thus doesn’t break any international trade rule. This argument, however, has not convinced other countries who point out that, among other things, the Centre and the State governments in India mandate the minimum price (the Fair and Remunerative Price, or FRP) at which sugar mills can buy sugarcane from farmers. In fact, in August last year, the Centre set the FRP at ₹290 per quintal and called it the “highest ever” FRP for sugarcane procurement. Individual States also set minimum procurement prices that may be higher than the Centre’s price to adjust for conditions at the local level.

The high procurement price for sugarcane set by the Government is believed to have led to a supply glut that in turn has caused sugar prices to drop. In fact, several sugar mills are caught in a debt trap as consumer demand for sugar has remained stagnant. The low price of sugar has affected the revenues of mills, their ability to pay farmers and also forced many mills to shut down. To help the sugar sector, the Centre has even mandated the compulsory blending of ethanol derived from sugarcane with fuels such as petrol and diesel. According to the Food Ministry, the country’s sugar production is likely to remain flat at 30.5 million tonnes in the next 2021-22 season as more sugarcane will be diverted for ethanol making.

State governments and the Centre have also regularly intervened to reduce the debt burden on sugar mills. Earlier this month, the Centre decided to restructure loans worth over ₹3,000 crore offered to sugar mills by the Sugar Development Fund. Without such assistance, it may not be possible for sugar mills to procure sugarcane from farmers at the minimum prices dictated by the government. Further, the Centre also regularly sanctions funds to encourage sugar mills to export sugar depending on sugar prices in the global market. In the budget last year, the Centre allocated a total of ₹3,500 crore to fund the export of 6 million tonnes of sugar.

What lies ahead?

The WTO Appellate Body’s decision will be considered final on the dispute. In case India refuses to comply with the decision, it might have to face retaliatory action from other countries. This could be in the form of additional tariffs on Indian exports and other stringent measures. Incidentally, the appellate body of the WTO is not functioning because of differences among member countries to appoint members, and disputes are already pending with it. The U.S. had blocked the appointment of members.

What is the WTO?

• The World Trade Organization (WTO) is the only global international organization dealing with the rules of trade between nations.
• Its main function is to ensure that trade flows as smoothly, predictably and freely as possible.
• WTO is not a United Nations specialized agency and it is not part of the United Nations system, but has cooperative arrangements and practices with the United Nations.
• The WTO has over 160 members representing 98 per cent of world trade.

 History of WTO

• From 1948 to 1994, the GATT (General Agreement on Tariffs and Trade) provided the rules for world trade.
• It seemed well-established but throughout those 47 years, it was a provisional agreement and organization.
• The WTO’s creation in 1995 marked the biggest reform of international trade since the end of the Second World War.
• Whereas the GATT mainly dealt with trade in goods, the WTO and its agreements also cover trade in services and intellectual property.
• The birth of the WTO also created new procedures for the settlement of disputes.

WTO functions

• WTO operates a global system of trade rules.
• WTO acts as a forum for negotiating trade agreements.
• WTO settles trade disputes between its members and
• WTO supports the needs of developing countries.

 WTO Decision-making

• The WTO’s top decision-making body is the Ministerial Conference. Below this is the General Council and various other councils and committees.
• Ministerial conferences usually take place every two years.
• The General Council is the top day-to-day decision-making body. It meets a number of times a year in Geneva.

 Director-General of the WTO

• Ngozi Okonjo-Iweala is the seventh Director-General of the WTO. She took office on 1 March 2021.
• She is the first woman and the first African to serve as Director-General. Her term of office will expire on 31 August 2025. 

WTO Principles

Below two principles are the foundation of the multilateral trading system.

Most-favoured-nation (MFN)

• ·         It means treating other people equally.
• Under the WTO agreements, countries cannot normally discriminate between their trading partners.
• If a country grants some country a special favour (such as a lower customs duty rate for one of their products), it has to do the same for all other WTO members.
• Exceptions:
  • if a country has Free Trade Agreement with some country;
  • if a country is giving developing countries special access to their markets;
  • if a country has raised barriers against products that are considered to be traded unfairly from specific countries.

National treatment

• ·         It means treating foreigners and locals equally.
• Imported and locally-produced goods should be treated equally — at least after the foreign goods have entered the market.
• The same should apply to foreign and domestic services, and to foreign and local trademarks, copyrights and patents.
• National treatment only applies once a product, service or item of intellectual property has entered the market. Therefore, charging customs duty on an import is not a violation of national treatment even if locally-produced products are not charged an equivalent tax.

 WTO dispute settlement

• WTO also deals in Dispute Settlements.
• One contravention of WTO agreements, a member country approaches the WTO’s dispute settlement body.
• All the members are encouraged to settle the disputes through consultation or through a panel, if the consultation fails.
• The WTO panel circulates the verdict of the dispute settlement amongst WTO members who can decide to either accept or reject the ruling.
• If the ruling is approved, the member country that violated the rules must change rules in line with the WTO Agreement.
• In the case of failure to do so, the complaining country and the violating country may determine a mutually-acceptable compensation, failing which, the complaining country may retaliate suitably.

 WTO settlement bodies

• The General Council convenes as the Dispute Settlement Body (DSB) to deal with disputes between WTO members.
• Appeals are handled by the permanent seven-member Appellate Body which is set up by the Dispute Settlement Body and broadly represents the range of WTO membership.